Several women, other than wives of presidents, have been recognized as being a "First Lady". This situation has arisen due to the President being a bachelor or widower, when the position was then filled by a female relative or friend of the President. Less commonly, the First Lady has delagated her duties to another woman when she is unable or unwilling to fulfill them herself.

The First Lady is not an elected position, carries no official duties, and brings no salary. Nonetheless, she attends many official ceremonies and functions of state either along with or in place of the President. Furthermore, many have taken an active role in campaigning for the President they are associated with. Hillary Rodham Clinton took the role one step further when she was, for a time, given a formal job in the Clinton administration to develop reforms to the health care system.

If the United States were to have a female President, it is not clear who would take the position of First Lady. A female president could act as her own First Lady, select a female relative or friend to occupy the role, or have her husband act as an analogous "First Gentleman".

The wife of the president is referred to by her married name - the couple is formally referred to as, for example, "The President and Mrs. Washington."

The term is also used to describe the wife of other government officials, or for a woman who has acted as a leading symbol for some activity (as in "First Lady of California" or "First Lady of Jazz" respectively).